2-{[2-(3-Chlorophenylamino)pyrimidin-4-ylamino]methyl}-piperidine-1-carboxylic acid tert-butyl ester → N2-(3-chlorophenyl)-N4-piperidin-2-ylmethyl-pyrimidine-2,4-diamine
Reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[CH2:14][NH:15][C:16]1[CH:21]=[CH:20][N:19]=[C:18]([NH:22][C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[CH:24]=2)[N:17]=1)=O)(C)(C)C>FC(F)(F)C(O)=O>[Cl:29][C:25]1[CH:24]=[C:23]([NH:22][C:18]2[N:17]=[C:16]([NH:15][CH2:14][CH:9]3[CH2:10][CH2:11][CH2:12][CH2:13][NH:8]3)[CH:21]=[CH:20][N:19]=2)[CH:28]=[CH:27][CH:26]=1Participants
Procedure
2-{[2-(3-chlorophenylamino)pyrimidin-4-ylamino]methyl}-piperidine-1-carboxylic acid tert-butyl ester, 15, is dissolved in neat trifluoroacetic acid (3 mL) and stirred at room temperature for 3 hours. The reaction is concentrated in vacuo and the residue partitioned between EtOAc and sat. NaHCO3. The organic layer is dried (MgSO4), concentrated in vacuo, and purified over silica (MeOH/CH2Cl2) to afford 7 mg (7% yield) of the desired compound: 1H NMR (CDCl3, 300 MHz) δ 1.50-1.63 (m, 1H), 1.70-1.92 (m, 4H), 1.95-2.10 (m, 2H), 2.88 (dt, J=12.0, 3.6 Hz, 1H), 3.30-3.40 (m, 1H), 3.52 (d, J=12.0 Hz, 1H), 3.61-3.70 (m, 1H), 3.87 (d, J=15.3 Hz, 1H) 6.01 (d, J=6.6 Hz, 1H), 7.02 (dt, J=7.5, 1.8 Hz, 1H), 7.22 (t, J=7.8 Hz, 1H), 7.25 (t, J=1.8 Hz, 1H), 7.75 (d, J=6.6 Hz, 1H), 7.96 (t, J=1.8 Hz, 1H); HRMS calcd for C16H20ClN5, 318.1485 m/z (M+H)+; observed 318.1481 m/z.
Workup
- concentrationThe reaction is concentrated in vacuo
- customthe residue partitioned between EtOAc and sat. NaHCO3
- dry with materialThe organic layer is dried (MgSO4)
- concentrationconcentrated in vacuo
- custompurified over silica (MeOH/CH2Cl2)
Sources & evidence
- ORD record
- ord-d4dbd7bbf64e46e295b4915dd5b6a748
- Source dataset
- uspto-grants-2013_01
- Patent number
- US08354407B2
Reaction notes
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